fertilidad y artritis reumatoidea

1. Vol.:(0123456789)
1 3
Inflammation Research
https://doi.org/10.1007/s00011-020-01362-w
REVIEW
Fertility and infertility implications in rheumatoid arthritis; state
of the art
Abolfazl Fattah1
· Amirhooman Asadi2
· Mohammad Reza Hooshangi Shayesteh3
· Forough Hatefi Hesari4
·
Sirous Jamalzehi5
· Mojtaba Abbasi6,7
· Mohammad Javad Mousavi8,9
· Saeed Aslani9
Received: 24 February 2020 / Revised: 28 April 2020 / Accepted: 14 May 2020
© Springer Nature Switzerland AG 2020
Abstract
Background A bulk of investigations imply that women with rheumatoid arthritis (RA) deliver fewer children in comparison
to healthy women.
Purpose This review article attempts to clarify the involvement of infertility-related issues in both RA men and women.
Moreover, the effect of RA disease on the fertility quality and quantity will be discussed.
Results Declined fertility rate in RA women seems to stem from modified inflammatory settings, advanced maternal age,
limited sexual activity, and adverse effects of drugs on ovarian function. Women with RA may have smaller families and seem
to be slower to conceive relative to their peer women. The chance of gestation in RA women may drop due to suppressed
sexual function through pain and fatigue. In addition, treatment of RA women with non-steroidal anti-inflammatory drugs
(NSAIDs) may prevent ovulation and therefore hinder the conception.
Conclusions A complex interaction between RA disease and fertility related issues is present. Despite an increase rate
of infertility in RA females or males, the mechanisms involved in this outcome is still unknown. Plausible causes of the
decreased fertility rate in RA patients might be due to inflammatory cytokines, suppressed sexual activity, drug treatments,
mother age, personal choice, or a combination of these elements.
Keywords Rheumatoid arthritis · Fertility · Pregnancy · Inflammation
Introduction
Rheumatoid arthritis (RA) is characterized by immune dys-
regulation with the hallmark of chronic inflammation and
pain in several joints. Almost 1% of people suffer from RA
worldwide. RA commonly affects women more than men
Inflammation Research
Responsible Editor: John Di Battista.
* Mohammad Javad Mousavi
sm‑mousavi@razi.tums.ac.ir
* Saeed Aslani
s‑aslani@razi.tums.ac.ir
1
Research Center for Health Sciences and Technologies,
Semnan University of Medical Sciences, Semnan, Iran
2
Veterinary Medicine, Faculty of Veterinary Medicine, Karaj
Branch, Islamic Azad University, Karaj, Iran
3
Department of Toxicology and Pharmacology, Faculty
of Pharmacy, Tehran University of Medical Sciences, Tehran,
Iran
4
Department of Microbiology, Islamic Azad University East
Tehran Branch, Tehran, Iran
5
Department of Medical Laboratory Sciences, Iranshahr
University of Medical Sciences, Iranshahr, Iran
6
Veterinary Medicine, Faculty of Veterinary Medicine,
Shahrekord Branch, Islamic Azad University, Shahrekord,
Iran
7
Reproductive Biotechnology Research Center, Avicenna
Research Institute, ACECR, Tehran, Iran
8
Department of Hematology, Faculty of Allied Medicine,
Bushehr University of Medical Sciences, Bushehr, Iran
9
Department of Immunology, School of Medicine, Tehran
University of Medical Sciences, Tehran, Iran

2. A. Fattah et al.
1 3
in the young period of life, in which decisions are made to
have child. Nonetheless, it appears to be more tough for RA
women to be conceived due to the disease complications
and/or therapy with non-steroidal anti-inflammatory drugs
(NSAIDs) [1–3].
It has been suggested that RA symptoms and mani-
festations are alleviated during gestation [4, 5]. On the
other hand, the postpartum period has been attributed to
be accompanied with exacerbated symptoms, due to the
elimination of immunomodulatory effects caused by fetal
antigens and pregnancy hormones [6, 7]. The precise link
between RA and fertility is yet to be divulged. Consider-
ing the three times high prevalence of RA in women [8]
and that diagnosis of remarkable number of these women
occurs during their reproductive period, it is postulated that
RA declines a couple’s potential to succeed in childbear-
ing. Moreover, it is still unclear whether RA itself or related
therapeutic drugs might impress childbearing, and also given
the association between RA and family size, it is a question
if decreased family size is because of RA effect on fertility
[9] or because of patients’ choice, or a combination of these
factors is involved. On the other hand, approximately two-
thirds of RA women use effective approaches of contracep-
tion, which might due to of an advise from their physician
with respect to weak potential of these patients in pregnancy
and successful delivery [10] (Fig. 1).
Several large cohorts have demonstrated that RA women
possess smaller families and have lower rate of conceiv-
ing potential. It seems that other than a personal choice in
limiting the family size, infertility also plays a critical role.
Pain and fatigue in RA women might be important factors in
suppressing the sexual function that may impress the chance
of gestation. In addition, NSAIDs have been associated with
decreased ovulation rate and these drugs should be used with
caution in such patients [11]. In this review article, the cross-
talk between RA disease and the fertility circumstances will
be discussed.
Rheumatoid arthritis family size
Women who are diagnosed with RA early in life have been
reported to have less children compared with those who
diagnosed at later ages in life. According to the study which
used questionnaire through calling to cases, 411 women with
RA were evaluated. The study reported that 8% of women
had been recommended to decrease their family size, and
20% reported their RA diagnosis impressed their decision
on being conceived and having children [12]. Addition-
ally, it was demonstrated that women with RA diagnosis
before 30-years-old had decreased number of children in
comparison to those whose diagnosis were happened after
30-years-old [1]. This study concluded that family size was
under the impression of RA disease activity. In addition, a
study evaluated the reproductive history questionnaire and
found that more than one‐half of young women with RA
had fewer children than it hoped to be [13]. The family size
is under the impression of RA disease in women. Effects of
different medication for RA disease on offspring need to be
Fig. 1 The crosstalk between RA disease and the fertility/infertility.
Several factors attributed in RA subjects may affect fertility condi-
tions. Among these factors, are decreased quality of life, decreased
sexual desire, and personal choice due to pain and fatigue. Drugs
used in RA therapy, such as NSAIDs may impress the fertility factors
such as ovulation in the patients. Moreover, treatment with metho-
trexate in RA patients may impress the AMH level and, thereby, the
ovarian reserve in the patients. Despite an unknown cause, the devel-
opment of autoimmune disorders, such as RA may prevalently be
seen in infertile subjects

3. Fertility and infertility implications in rheumatoid arthritis; state of the art
1 3
controlled by training of physicians as well as patients. Safe
medical choices during pregnancy should be considered that
are beneficial in managing the disease activity as well as to
prevent adverse impressions for the fetus. As a consequence,
to contribute women establishing their childbearing aims, it
is mandatory to improve patient education and consider the
underlying factors involved in the infertility and pregnancy
loss.
Rheumatoid arthritis ovarian function
It is not completely understood if an increased amount of
time to gestation is attributed to weak ovarian function in RA
women. The ovarian granulosa cells release anti-Müllerian
hormone (AMH), which is a marker evaluated for ovarian
reserve. It was reported that AMH was lower in RA women.
Nonetheless, no difference in anovulation was detected.
Furthermore, the infertility prevalence was observed to be
similar between RA and control women. The infertility was
contemplated to stem from polycystic ovary syndrome in
healthy controls. However, it was not revealed that what
could be the underlying cause of infertility in women with
RA [14]. Considering the predominance of methotrexate
therapy in RA patients, it is suggested that this medication
could negatively affect the ovarian reserve. In addition, a
study evaluated the AMH level in recently diagnosed RA
women and compared it to that of healthy subjects. The
study indicated that there was no significantly decreased
level of AMH in RA women. It should be noted that this
study had evaluated 72 RA cases, in which 31 patients were
treated with methotrexate [15], adding the complexity of
disclosing the puzzle of methotrexate role in affecting the
ovarian reserve and infertility in RA women. The difference
in AMH level implies that there might be different mecha-
nisms by which the disease affects the infertility. As a result,
despite smaller family sizes and increased time to gestation
in RA women, it seems that ovarian reserve might not be
affected by the disease according to AMH level.
Pregnancy loss in RA
Although early miscarriage, represented through a preg-
nancy loss before 10 weeks of gestation, is commonly
reported in the general population, both fetal losses,
represented by a pregnancy loss more than 10 weeks of
gestation, and stillbirth, with pregnancy loss more than
20 weeks of gestation, are not typically reported. Retro-
spective data are still limited to clearly demonstrate the
prevalence and risk of miscarriage in RA women. A study,
evaluating 40 women with RA, indicated that there was
no significantly increased miscarriage rate in women with
RA [16]. Furthermore, in a study, in which 195 women
with RA were investigated, no significant increase was
detected in the rate of spontaneous abortion. However,
the study reported an increase, but not significant, in
stillbirth rate [17]. A cohort study on nationwide Dan-
ish health registries, evaluating women with an embryo
transfer during 1994–2017, indicated that the chance of a
live birth was remarkably lower in RA women receiving
assisted reproductive technology treatment in compari-
son to women without RA, originating from an impaired
chance of embryo implantation [18]. There are still lit-
tle investigations with respect to pregnancy loss in RA
women, however, it should be taken seriously.
RA and preeclampsia
Hypertension and preeclampsia have been thought to be
frequently occurred during gestation of RA women. By
evaluating 1425 deliveries in RA women from the United
States, it was found that there was increased rate of hyper-
tension and related issues in RA cases relative to healthy
controls [19]. Taiwan’s National Health Insurance (NHI)
reported that there was an odds ratio (OR) of 2.22 in the
development of preeclampsia in RA women [20]. How-
ever, these studies did not consider the effects of diseases
activity, age, or drug treatment on the hypertension-related
complications. On the other hand, a study with small sam-
ple size of evaluating 133 pregnancies in RA women, did
not show preeclampsia in the cases. However, there were
five cases who had referred to the hospital, suffering from
hypertension [21]. By evaluating the 2003–2011 Nation-
wide Inpatient Sample of Healthcare Cost and Utiliza-
tion Project, 42.32 million obstetric hospitalized women
were evaluated, of which 31,439 women had RA. It was
observed that maternal RA subjects had a remarkably
higher prevalence of complications occurring during preg-
nancy, including antepartum hemorrhage, hypertensive
diseases, premature rupture of membranes, preterm deliv-
ery, intrauterine growth retardation, and cesarean delivery
[22]. Another large cohort study reported that women with
RA were more likely to develop pre-eclampsia, eclampsia,
gestational diabetes, to present with preterm premature
rupture of membranes, to experience placental abruption
and placenta previa, and to deliver by cesarean section.
Postpartum, RA-complicated pregnancies were related
to wound complications as well as thromboembolisms.
Furthermore, congenital anomalies, small for gestational
age and preterm birth were more common in offspring
from RA women [23]. It appears that RA women have an
increased risk of adverse complications related to preg-
nancy and, therefore, an immediate monitoring is required
before and after delivery to decrease adverse events. Fur-
ther studies are mandatory to test for the pregnancy out-
comes in relation to the severity of RA.

4. A. Fattah et al.
1 3
Inflammation and infertility in RA women
Although it is a new subject of study, the involvement of
inflammation in the process of gestation and fertility is
controversial. It has been reported that the disease activ-
ity of RA women was improved in 60% of subjects with
RA during pregnancy, while it was flared in 46.7% post-
partum subjects, implying to the effect of altered profile
of hormones and cytokines to RA during pregnancy [24].
During the menstrual cycle, complicated interactions occur
between the endocrine and immune systems that is critical
for suitable mechanobiology of the reproductive system in
females. Prostaglandin production, which is mediated by the
function of cyclooxygenase enzymes (COX-1 and COX-2),
is involved in several functions of reproductive system, such
as ovulation and implantation. Throughout the menstrual
cycle, prostaglandin levels are decreased and increased in
a cyclic pattern, and like several cytokines, their produc-
tion is different in response to sexual hormones, such as
estrogen and progesterone [25–28]. The role of prostaglan-
din in proper implantation of the blastocyst in the uterus
endometrium has been indicated [29]. It has been shown
that prostaglandin take part in the natural function of ovary
and follicles, including cumulus granulosa cell growth and
degradation of the extracellular matrix of the ovary [30–34].
Studies have shown that inhibition of COX-2 enzyme can
hinder the follicle rupture and ovulation process [35–37].
Furthermore, cytokines and other inflammatory mediators
are involved in the process of endometrial receptivity [38], in
which endometrium should have appropriate conditions and
react suitably to blastocyst implantation [26, 39]. Despite
some important roles by cytokines and prostaglandins in
the normal reproductive cycle, studies have not clearly dem-
onstrated the participation of these mediators in the con-
text of RA. However, considering the role of hormones and
inflammatory products of COX enzymes, further studies are
needed to divulge the effect of such elements on the quality
and quantity of fertility in RA women.
Fertility in female RA patients
RA women encounter difficulties in conceiving and expe-
rience longer time to pregnancy. Moreover, it has been
reported that 25–42% of women with RA did not become
pregnant within 1 year [40]. Although non-significant dif-
ference, but a positive history of infertility was found in 22
(44%) Nigerian RA patients and 14 (28%) controls, history
of irregular menstruation was detected in 15 (30%) of RA
patients in comparison to four (8%) controls [41]. Different
contributing factors might be involved with the impaired
fertility in RA women. In women RA patients, earlier meno-
pause has been seen [11]. Although there is evidence that
adversely advice the attribution of ovarian reserve with
AMH level [15], a study indicated that AMH level was
declined in established RA. This observation implies that
ovarian reserve decreases secondary to the development of
RA disease. Disease activity has been reported to be associ-
ated with impaired fertility in RA women. It was reported
that 67% of women having a Disease Activity Score-28
(DAS-28) more than 5.1, which represents active disease,
had a long time to pregnancy (more than 1 year), while only
30% of women in remission phase, represented through
DAS28 score less than 2.6, experienced more than 1 year
time to pregnancy [40].
Drug treatment, such as NSAIDs and prednisone, have
also been demonstrated to affect the time to pregnancy
[40, 42]. Moreover, therapy with glucocorticoids influence
on fertility through by direct modulation of the ovarian
function and endometrium or transient repression of the
hypothalamic–pituitary–ovarian axis [43, 44]. Decreases
sexual activity might also impress the fertility in women
RA patients [11]. Most of these investigations has been
performed on RA women in postmenopausal phase, and
therefore it is unclear if these observations are also true for
younger women with RA, who have tendency for gestation
[11].
Fertility in male RA patients
Little is studied about fertility findings and pregnancy issues
in male RA patients. It has been observed that male RA
patients have lower levels of testosterone; however, the effect
of this decreased testosterone levels have not been investi-
gated on fertility [45]. Furthermore, the effects of medica-
tions in male RA patients on fertility circumstances have
not been investigated. The disease-modifying antirheumatic
drug (DMARD), sulfasalazine, has been observed to cause
decreased sperm motility, oligospermia, and high rates of
sperms with abnormal morphology [46]. However, drug
withdrawal was reported to eventuate in improving of sper-
matogenesis after 2 months [46]. It has been suggested that
therapy with methotrexate is better to be stopped at least
3 months before deciding to plan for pregnancy [47]. None-
theless, in a study with small sample size, it was observed
that paternal use of low-dose of methotrexate was not
resulted in an increased risk of abnormalities in child [48,
49]. Despite oligospermia in case reports, it seems that low
dose of methotrexate is not associated with decreased semen
quality and quantity in RA males [50]. Initial investigations
suggested that RA therapy with tumor necrosis factor (TNF)
blockers in males decreased quality of sperm; nevertheless,
further studies indicated that TNF blockers did not result
in aberrant male fertility quality and quantity as well as
increased risk of impaired pregnancy-related complications
[51–53]. Furthermore, male RA therapy with NSAIDs and
glucocorticoids may cause impaired male fertility [54, 55].

5. Fertility and infertility implications in rheumatoid arthritis; state of the art
1 3
Alternately, it has been demonstrated, through in vitro stud-
ies, that chloroquine may impair sperm motility [50].
Influence on child
In general, studies have reported no enhanced risk of con-
genital complications or death cases after delivery in chil-
dren born from RA women [56, 57]. Nonetheless several
reports show an increased risk of small-for-gestational-age
infants in women with RA [20, 57–59]. There is evidence
reporting the effect of RA disease on the methylation of
children born to mothers with RA [60]. Moreover, it was
indicated that increased disease activity of RA women dur-
ing gestation was linked to lower birth weight in children,
despite the mean weight was still included in the normal
range [61]. Decreased birth weight has been observed to
be associated with enhanced risk of metabolic disease and
cardiovascular complications during adulthood [62, 63]. It
was observed that 28% of children born from RA women
presented fast gaining weight, which was linked to disease
activity of mother with RA [64]. Nonetheless, after monitor-
ing these children after 7 years, no evidence of increased risk
of cardiovascular complications, such as high blood pres-
sure, was identified [65]. A large prospective study indi-
cated that RA was associated with decreased proportions of
women breastfeeding their kids and earlier cessation, mainly
due to restart of medication for their RA disease [66]. This
issue might impress the growth of children, and might lead
to adulthood complications.
RA therapy and infertility
The recent guidelines from the British Society for Rheuma-
tology (BSR) and British Health Professionals in Rheuma-
tology (BHPR), and the European League Against Rheuma-
tism (EULAR) has led to development of Saint Vincent’s
University Hospital/National Maternity Hospital consensus
protocol for evidence-based medication during pregnancy
in RA patients. Several antirheumatic drug options during
pregnancy and breastfeeding are currently available, such as
antitumor necrosis factor (anti-TNF) biologic drug [67]. In
fact, anti-TNF biologics seem to be promising for maintain-
ing remission in RA patients and may be prescribed in the
first half of pregnancy at least [68].
Glucocorticoids
Glucocorticoids, like prednisone, are metabolized in the
placenta in a large amount and, hence, the amount of the
drug that reaches to the fetus is below than 10%. Glucocor-
ticoids are generally not regarded as teratogenic agents [69,
70]. That notwithstanding, utilization of glucocorticoids has
been attributed with limitations in the intrauterine growth,
premature membranes rupture, and shorter gestational age
and, therefore, should be used with caution and minimized
[69, 70]. It has been suggested that using glucocorticoids is
not interfering with breastfeeding [71].
Disease‑modifying antirheumatic drugs
Methotrexate is a DMARD that has been reported to be tera-
togenic, which triggers miscarriages and is strongly sug-
gested to be limited during pregnancy in RA patients [69,
72]. It is generally recommended to cease using methotrex-
ate at least 3 months prior to a gestation [47]. It has been
established that methotrexate is detectable in the breast milk
in little amounts and is recommended to stop medication by
this drug during breastfeeding [69].
As a DMARD, leflunomide has been reported to be tera-
togenic in animal models [73]. Human studies, on the other
hand, has indicated that there was no a significant increased
risk of adverse pregnancy outcomes [74] in women used
leflunomide who also had cholestyramine elimination pro-
cedure during early periods of pregnancy [75].
Hydroxychloroquine has been shown to be able to crosses
through placenta; nonetheless, reports indicated no increase
in congenital malformations of gestations at the recom-
mended dose, namely 200–400 mg daily. In addition, no
developmental abnormalities in children born from mothers
with hydroxychloroquine medication have been reported in
long-term follow-up studies [69, 71]. The amount of hydrox-
ychloroquine detected in the breast milk is little and, as a
result, it is regarded to be safe during breastfeeding [69, 71].
Despite sulfasalazine can cross the placenta, studies have
reported that sulfasalazine can be used safely in the pregnant
women, in a dose less/equal than 2 g daily [69]. Sulfasala-
zine has been shown to prevent the gastrointestinal uptake
of folate and, hence, it is recommended to use folate supple-
mentation throughout pregnancy in patients under therapy
with sulfasalazine. This drug has been detected in small con-
centrations in the breast milk. Although the metabolites of
sulfasalazine are found in the serum of 30–60% of pregnant
women, it is safe during breastfeeding [71].
Studies have shown that cyclosporine and azathioprine
are safe during gestation; that notwithstanding, due to
unprofitable benefit–risk balance, there prescription in preg-
nant RA women is limited [69].
TNF blockers
Most data about the use of TNF blockers in pregnant RA
cases are related to adalimumab and infliximab, and then
etanercept and certolizumab. Data from a large prospective
study revealed that there was a little enhance in the main
congenital disabilities after treatment with TNF blockers in
the first trimester of pregnancy. Nonetheless, the study could

6. A. Fattah et al.
1 3
not find important malformations [76]. Additionally, the use
of TNF blockers could not be associated with the congeni-
tal abnormalities as well as unwanted pregnancy presenta-
tions [77]. Etanercept was the preferred TNF blocker in RA
women [78]. The AbbVie safety database report in Japan
revealed that no additional risk to pregnancy outcomes with
adalimumab exposure, despite inconclusive safety concerns
[79].
At the week 18 of pregnancy, TNF blockers that are com-
posed of the fragment crystallizable (Fc) region of an IgG
antibody are actively crossed from the maternal blood to the
fetal circulation [80]. It has been reported that serum levels
of infliximab and adalimumab can be up to 3 times increased
in the newborn after the third trimester exposure in compari-
son to the mother [81]. Crossing of etanercept and certoli-
zumab through placental has less been of concern [81, 82].
Exception than certolizumab, it is recommended to delay
all live vaccines for a newborn until 6 months who have
exposure to TNF blockers in the third trimester of gesta-
tion [83]. According to the EULAR recommendations, it has
been advised to consider resuming the use of TNF blockers
in the first part of gestation. Because of low rates of trans-
placental cross, etanercept, and certolizumab may be safe
and considered for prescription throughout pregnancy [71].
Owing to ignorable cross into breast milk, TNF block-
ers, including adalimumab, infliximab, certolizumab, and
etanercept are safe in breastfeeding [71].
NSAIDs
The primary mechanism of NSAIDs, which is widely used in
RA patients, action is to inhibit the COX system and, there-
fore, blocking of prostaglandin production [84]. Over the
course of the past few decades, there have been inconsistent
recommendations on the use of NSAIDs during gestation.
Despite the NSAIDs labeling as category B drugs during
pregnancy by the Food and Drug Administration (FDA),
the discontinuation of NSAIDs use in the third trimester
is recommended [85], because of worries with respect to
premature closure of the ductus arteriosus during the fetus
development. Studies on the RA patients have suggested
stopping the NSAID use at least 32 weeks of pregnancy
age [86, 87].
A bulk of data have addressed to the potential impres-
sion of NSAIDs on the implantation and fertility. Early
in 1996, the case reports revealed a possible association
between NSAID use in the RA patients and fertility impair-
ments [88–90]. However, Danish birth-registry study in
2001 reported no significant increase in the unwanted birth
outcomes; however, a high miscarriage rate was observed
with the use of NSAIDs [91]. Moreover, it was revealed
that miscarriage risk was increased with use of NSAIDs in
a study of 1000 pregnant women [92]. A Canadian study in
2011 also reported same outcomes [93].
The proposed mechanism of NSAIDs involvement in the
miscarriage and infertility is probably because of prosta-
glandin production suppression that impresses ovulation
[34] and implantation [92]. Animal studies have revealed
that COX-2 inhibitors may interfere with ovulation. NSAID
use during ovulation was associated with ovulation in only
the 25% or fewer women [94]. Furthermore, it was reported
that NSAIDs postponed the ovulation by about 5 days [95].
Moreover, an association was found between NSAID use
and nulliparity [96].
Concluding points
Nowadays, there is a complex interaction and relationship
between RA disease and fertility related issues. Although a
bulk of studies has proposed an increase rate of infertility
in RA females or males, the causal mechanisms underlying
this outcome is a matter of conundrum. However, it has been
postulated that the decreased fertility rate in RA patients
stems from inflammatory cytokines, suppressed sexual activ-
ity, drug treatments, mother age, personal choice, or a com-
bination of these factors simultaneously. On the other side,
infertile men have been reported with an increased risk of
developing autoimmune disorders, including multiple scle-
rosis, psoriasis, thyroiditis, Grave’s disease, and RA [97].
The use of normal medications in the RA patients has been
accompanied with some limitations; however, several bio-
logicals have been reported to be safe during pregnancy as
well as breastfeeding period. In spite of attempting to dis-
close the mechanobiology of infertility, physicians recom-
mend some points in RA patients, including withdrawing
NSAIDs receiving before and during gestation.
Author contributions AF Participated in manuscript preparation and
read the manuscript critically. SN Participated in manuscript prepara-
tion and read the manuscript critically. MRHS Participated in manu-
script preparation and read the manuscript critically. FHH Participated
in manuscript preparation and read the manuscript critically. SJ Par-
ticipated in manuscript preparation and read the manuscript critically.
MA Participated in manuscript preparation and read the manuscript
critically. MJM Developed the main idea, participated in manuscript
preparation and read the manuscript critically. SA Developed the main
idea, participated in manuscript preparation, and read the manuscript
critically.
Funding Not applicable.
Compliance with ethical standards
Conflict of interest Abolfazl Fattah, Soheila Nouraei, Mohammad
Reza Hooshangi Shayesteh, Forough Hatefi Hesari, Sirous Jamalzehi,

7. Fertility and infertility implications in rheumatoid arthritis; state of the art
1 3
Mojtaba Abbasi, Mohammad Javad Mousavi, and Saeed Aslani de-
clare that they have no conflict of interest.
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